This program is designed to investigate the metabolism of psychotomimetic 1-phenyl-2-aminopropanes in an attempt to determine to what extent the disposition and biotransformation of these drugs contribute to their overall pharmacological and toxicological properties. Mechanistic details concerning the pathways leading to the formation of chemically reactive metabolites will be investigated. The biochemical-pharmacological and psychopharmacological properties of a select group of amines and specific metabolites suspected of possessing neurotoxic properties will be evaluated. Characterization of the interactions of the reactive metabolites with biopolymers and with model small molecule nucleophiles will be pursued. The effects of the putative neurotoxic metabolites on brain biogenic amines will be examined. Finally, we plan to explore the possibility that aberrant metabolic pathways of endogenous biogenic amines will generate neurotoxic substances with the potential to cause central biochemical lesions.